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We read with interest the recent article on the management of irritable bowel syndrome (IBS).1 The authors present an overview of the epidemiology, impact, aetiology, diagnosis, and management of IBS. Although the article is informative, we believe that several topics require clarification in light of current knowledge about the pathophysiology of IBS and treatment options for IBS patients.
AETIOLOGY: PSYCHOLOGICAL FACTORS
The authors mention that significant psychological symptoms prevail in IBS, particularly among patients referred to gastroenterology clinics. It is true that studies have shown that 54%–94% of patients seen in tertiary referral centres meet the criteria for at least one primary psychiatric disorder.2 However, only 25%–30% of patients with IBS actually seek care, and of those, fewer than 1% are referred to specialists.3,4 One study estimates that, in the community setting, the percentage of IBS patients with comorbid psychiatric disturbances is approximately 18%.5 Furthermore, psychiatric disorders have not been shown to be pathogenic for IBS.
AETIOLOGY: PHYSIOLOGICAL FACTORS
The authors acknowledge that altered somatovisceral sensitivity and gut motor dysfunction are possible pathophysiological mechanisms involved in IBS; however, they fail to discuss the role of 5-hydroxytryptamine (5-HT) and its receptors in gut motility, intestinal secretion, and visceral sensitivity.6 The vast majority of 5-HT in the body (95%) is stored in enterochromaffin cells and afferent enteric nerves of the gastrointestinal tract, where several 5-HT receptor subtypes have been identified. Substantial evidence underscores the essential role of 5-HT and its receptors, particularly the 5-HT3 and 5-HT4 subtypes, in the overall functioning of the gut.6
The authors state that targeted investigations are needed to exclude organic pathology when diagnosing patients with IBS. However, these tests are required only if “red flags” are present.7 Studies have shown that additional testing does not alter the rate of IBS diagnosis.8
The authors present a limited discussion on the use of 5-HT modulators in the treatment of IBS patients. Tegaserod (Zelmac/Zelnorm), which was approved by the US Food and Drug Administration in July 2002 and has also been approved in more than 65 countries worldwide, is indicated for the short term treatment of women with IBS whose primary bowel symptom is constipation. Tegaserod was one of only two IBS treatment options given a grade A recommendation—the most robust—for the treatment of women with IBS and constipation.7 Both the efficacy and the safety of tegaserod have been demonstrated consistently in several large, randomised, placebo controlled clinical trials (table 1). Treatment with tegaserod 6 mg twice daily resulted in significant global relief of IBS symptoms compared with placebo.
In summary, although some patients with IBS may have comorbid psychiatric disorders, physiological factors are the primary contributors to IBS pathophysiology and symptoms. Recent evidence indicates that 5-HT and its receptors play a critical part in the pathophysiology of IBS, and the highly selective 5-HT4 receptor agonist tegaserod has proved safe and effective in relieving the multiple symptoms of IBS in women with IBS-C.
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